Natalie K. Boyd

The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010

BACKGROUND Clostridium difficile infection (CDI) incidence is a growing concern. This study provides national estimates of CDI over 10 years and identifies trends in mortality and hospital length of stay (LOS) among hospitalized adults with CDI. METHODS We conducted a retrospective analysis of the US National Hospital Discharge Surveys from 2001-2010. Eligible cases included adults aged ≥ 18 years discharged from a hospital with an ICD-9-CM diagnosis code for CDI (008.45). Data weights were used to derive national estimates. CDI incidence rates were depicted as CDI discharges per 1,000 total adult discharges. RESULTS These data represent 2.2 million adult hospital discharges for CDI over the study period. CDI incidence increased from 4.5 CDI discharges per 1,000 total adult discharges in 2001 to 8.2 CDI discharges per 1,000 total adult discharges in 2010. The overall in-hospital mortality rate was 7.1% for the study period. Mortality increased slightly over the study period, from 6.6% in 2001 to 7.2% in 2010. Median hospital LOS was 8 days (interquartile range, 4-14 days), and remained stable over the study period. CONCLUSIONS The incidence of CDI among hospitalized adults in the United States nearly doubled from 2001-2010. Furthermore, there is little evidence of improvement in patient mortality or hospital LOS.

Utilization of omeprazole to augment subtherapeutic voriconazole concentrations for treatment of Aspergillus infections.

ABSTRACT Voriconazole is the preferred antifungal agent for Aspergillus infections. Therapeutic drug monitoring is recommended to achieve target concentrations and prevent toxicity. However, variable pharmacokinetics, cytochrome P450 polymorphisms, and extensive drug-drug interactions can contribute to subtherapeutic concentrations. We report a voriconazole “boosting” effect of omeprazole to achieve target concentrations for the treatment of Aspergillus in a patient who had persistently subtherapeutic trough concentrations.

In Vitro Study of the Variable Effects of Proton Pump Inhibitors on Voriconazole

ABSTRACT Voriconazole is a broad-spectrum antifungal agent used for the treatment of severe fungal infections. Maintaining therapeutic concentrations of 1 to 5.5 μg/ml is currently recommended to maximize the exposure-response relationship of voriconazole. However, this is challenging, given the highly variable pharmacokinetics of the drug, which includes metabolism by cytochrome P450 (CYP450) isotypes CYP2C19, CYP3A4, and CYP2C9, through which common metabolic pathways for many medications take place and which are also expressed in different isoforms with various metabolic efficacies. Proton pump inhibitors (PPIs) are also metabolized through these enzymes, making them competitive inhibitors of voriconazole metabolism, and coadministration with voriconazole has been reported to increase total voriconazole exposure. We examined the effects of five PPIs (rabeprazole, pantoprazole, lansoprazole, omeprazole, and esomeprazole) on voriconazole concentrations using four sets of human liver microsomes (HLMs) of different CYP450 phenotypes. Overall, the use of voriconazole in combination with any PPI led to a significantly higher voriconazole yield compared to that achieved with voriconazole alone in both pooled HLMs (77% versus 59%; P < 0.001) and individual HLMs (86% versus 76%; P < 0.001). The mean percent change in the voriconazole yield from that at the baseline after PPI exposure in pooled microsomes ranged from 22% with pantoprazole to 51% with esomeprazole. Future studies are warranted to confirm whether and how the deliberate coadministration of voriconazole and PPIs can be used to boost voriconazole levels in patients with difficult-to-treat fungal infections.

Regional and seasonal variation in Clostridium difficile infections among hospitalized patients in the United States, 2001-2010

BACKGROUND This study identified national regional and seasonal variations in Clostridium difficile infection (CDI) incidence and mortality among hospitalized patients in the United States over a 10-year period. METHODS This was a retrospective cohort study of the U.S. National Hospital Discharge Survey from 2001-2010. Eligible cases had an ICD-9-CM discharge diagnosis code for CDI (008.45). Data weights were used to derive national estimates. CDI incidence and mortality were presented descriptively. Regions were as defined by the U.S. Census Bureau. Seasons included the following: winter (December-February), spring (March-May), summer (June-August), and fall (September-November). RESULTS These data represent 2.3 million CDI discharges. Overall, CDI incidence was highest in the Northeast (8.0 CDIs/1,000 discharges) and spring (6.2 CDIs/1,000 discharges). CDI incidence was lowest in the West (4.8 CDIs/1,000 discharges) and fall (5.6 CDIs/1,000 discharges). Peak CDI incidence among children occurred in the West (1.7 CDI/1,000 discharges) and winter (1.5 CDI/1,000 discharges). Mortality among all CDI patients was highest in the Midwest (7.3%) and during the winter (7.9%). CONCLUSION The region and season with the highest CDI incidence rates among patients hospitalized in U.S. hospitals were the Northeast and spring, respectively. The highest CDI mortality rates were seen in the Midwest and winter. Children exhibited different regional and seasonal CDI variations compared with adults and older adults.

Predictors of community-associated Staphylococcus aureus, methicillin-resistant and methicillin-susceptible Staphylococcus aureus skin and soft tissue infections in primary-care settings.

Skin and soft tissue infections (SSTIs) due to Staphylococcus aureus have become increasingly common in the outpatient setting; however, risk factors for differentiating methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) SSTIs are needed to better inform antibiotic treatment decisions. We performed a case-case-control study within 14 primary-care clinics in South Texas from 2007 to 2015. Overall, 325 patients [S. aureus SSTI cases (case group 1, n = 175); MRSA SSTI cases (case group 2, n = 115); MSSA SSTI cases (case group 3, n = 60); uninfected control group (control, n = 150)] were evaluated. Each case group was compared to the control group, and then qualitatively contrasted to identify unique risk factors associated with S. aureus, MRSA, and MSSA SSTIs. Overall, prior SSTIs [adjusted odds ratio (aOR) 7·60, 95% confidence interval (CI) 3·31-17·45], male gender (aOR 1·74, 95% CI 1·06-2·85), and absence of healthcare occupation status (aOR 0·14, 95% CI 0·03-0·68) were independently associated with S. aureus SSTIs. The only unique risk factor for community-associated (CA)-MRSA SSTIs was a high body weight (⩾110 kg) (aOR 2·03, 95% CI 1·01-4·09).

Application of a Risk Score to Identify Older Adults with Community-Onset Pneumonia Most Likely to Benefit From Empiric Pseudomonas Therapy

To assess the impact of empiric Pseudomonas pharmacotherapy on 30‐day mortality in hospitalized patients with community‐onset pneumonia stratified according to their risk (low, medium, or high) of drug‐resistant pathogens.